Abstract 3424: Genomic alterations in clonal hematopoiesis

Abstract

Abstract Cancer development is an incremental process. Mutations that initiate clonal hematopoiesis often arise in individuals many years before disease symptoms are apparent. We discovered blood somatic mutations in 8,612 germline blood samples in The Cancer Genome Atlas, drawing fundamental distinctions between these events and germline variants. In a preliminary scan of 5,949 samples, 13,345 blood-specific mutations were identified, preferentially distributed across 26 genes, including ones frequently mutated in hematologic malignancies (e.g., DNMT3A, ASXL1, TET2, JAK2, IDH2, SF3B1, MLL3, and KDM6A) and genes rarely mutated in primary hematologic tumors, including EGFR, PIK3CA, NOTCH2, and PPM1D. Further, we utilized both exome sequencing and SNP array data to conduct the first large-scale survey of blood somatic copy number variation, discovering potentially oncogenic events such as JAK2 amplification. Finally, elderly individuals and smokers have increased likelihoods of undergoing clonal expansion. Our analysis of genomic alterations reveals the origins of hematologic malignancies and can facilitate advancement in early detection and prevention. Citation Format: Kuan-Lin Huang, Mingchao Xie, Yige Wu, Reyka Jayasinghe, Rajees Varghese, R. Jay Mashl, Song Cao, Matthew Wyczalkowski, Wen-wei Liang, Michael C. Wendel, Ryan Fields, Michael D. McLellan, Daniel C. Link, Feng Chen, Li Ding. Genomic alterations in clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3424.